Xiaoying Lü

Southeast University (China), Nan-ching-hsü, Jiangxi Sheng, China

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Publications (23)85.26 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this study is to investigate the mechanism of the effects of gold nanoparticles (GNPs) on human dermal fibroblasts (HDFs) at the microRNA level. First, 20-nm GNPs were synthesized and their effect on HDF proliferation was assayed. SOLiD sequencing technology was then utilized to obtain the microRNA expression profile after GNP treatment. The microRNA expression data were compared with previously obtained mRNA and protein expression data to identify the microRNA target mRNAs/proteins. Moreover, bioinformatics analyses and validation experiments were conducted. Lastly, the roles of GNPs and silver nanoparticle (SNPs) on HDFs were compared at the microRNA level. The results showed that GNPs were not cytotoxic as 202 microRNAs were differentially expressed after treatment with 200 μm GNPs for 1, 4 and 8 h. Bioinformatics analyses revealed that these dysregulated miRNAs mainly functioned in metabolic processes and participated in 71 biological pathways, including two key pathways in which the differentially expressed miRNA, target mRNAs and proteins were simultaneously joined, the mRNA processing pathway and MAPK signaling pathway. Biological experiments in cells confirmed that GNPs affected energy metabolism but did not induce apoptosis, destroy the cytoskeleton or induce reactive oxygen species (ROS) production. Comparing the mechanism of the effects of GNPs and SNPs on HDFs at the microRNA level, it was found that, unlike SNPs, GNPs impacted the cell cycle, weakened the ATP synthesis inhibition and cytoskeleton damage, suppressed apoptosis, and did not lead to cytotoxicity. The difference in ROS production by these two nanoparticles might partially explain the fact that GNPs showed no cytotoxic effects on HDFs, unlike SNPs.
    Biomaterials 10/2014; · 8.31 Impact Factor
  • Zhiwei Zhang, Jiandan Wang, Xiaoying Lü
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    ABSTRACT: This work combined transcriptomics, proteomics, and microRNA (miRNA) analyses to elucidate the mechanism of natural hydroxyapatite (NHA)-induced osteogenic differentiation of mesenchymal stem cells (MSCs). First, NHA powder was obtained from pig bones and fabricated into disc-shaped samples. Subsequently, the proliferation and osteogenic differentiation of MSCs cultured on NHA were investigated. Then, proteomics was employed to detect the protein expression profiles of MSCs cultured on NHA, and the effect of NHA on MSCs was analyzed through an integrated pathway analysis (including proteomics and previous transcriptomics data) in which specific NHA-induced differentiation pathways were analyzed. The pathway nodes with expression data at both the mRNA and protein levels (mRNA–protein pairs) were filtered in differentiation-related pathways. miRNAs corresponding to these target mRNA–protein pairs were predicted, screened and tested, and the regulatory effects of miRNAs on mRNA–protein pairs were analyzed. Finally, the NHA-induced osteogenic pathways were verified. The results of an MTT assay and alkaline phosphatase (ALP) staining showed that the cell proliferation rate decreased and the osteogenic performance improved in the presence of NHA. By integrating transcriptomics and proteomics, the genes and proteins involved in 89 pathways were shown to be differentially expressed. Among them, 5 differentiation-associated pathways, in which 9 miRNAs and 8 regulated-target mRNA–protein zby inhibiting the target mRNA–protein pair HSPA8 in the MAPK signaling pathway, and miR-26a and miR-26b might inhibit adipogenic differentiation by repressing the target mRNA–protein pair HMGA1 in the adipogenesis pathway. A verification experiment for the osteogenic pathway indicated that the ERK1/2 or JNK MAPK pathways might play an important role in NHA-induced osteogenic differentiation. In conclusion, NHA affected MSCs at both the transcriptional and translational levels, and MSC osteogenic differentiation eventually occurred through the MAPK and adipogenesis pathways, in which miRNAs and target mRNAs/proteins participated cooperatively.
    Biomedical Materials 06/2014; 9(4):045005. · 2.92 Impact Factor
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    ABSTRACT: The aim of this study is to systematically investigate the molecular mechanism of different effects of nickel titanium (NiTi) alloy surface and titanium nitride (TiN) coating on endothelial cell function. Release of nickel (Ni) ion from bare and TiN-coated NiTi alloys and proliferation of endothelial cells on the two materials were evaluated, and then influence of the two materials on cellular protein expression profiles was investigated by proteomic technology. Subsequently, proteomic data were analyzed with bioinformatics analyses and further validated using a series of biological experiments. Results showed that although the two materials did not affect cell proliferation, the Ni ions released from bare NiTi alloy generated inhibition on pathways associated with actin cytoskeleton, focal adhesion, energy metabolism, inflammation, and amino acid metabolism. In comparison, TiN coating not only effectively prevented release of Ni ions from NiTi alloy, but also promoted actin cytoskeleton and focal adhesion formation, increased energy metabolism, enhanced regulation of inflammation, and promoted amino acid metabolism. Furthermore, the two processes, “the initial mediation of adsorbed serum protein layer to endothelial cell adhesion and growth on the two materials” from our previous study, and “the following action of the two materials on cellular protein expression profile”, were linked up and comprehensively analyzed. It was found that in stage of cell adhesion (within 4 h), release of Ni ions from bare NiTi alloy was very low, and the activation of adsorbed proteins to cell adhesion and growth related biological pathways (such as regulation of actin cytoskeleton, and focal adhesion pathways) was almost as same as TiN-coated NiTi alloy. This indicated that the released Ni ions did not affect the mediation of adsorbed proteins to endothelial cell adhesion. However, in stage of cell growth and proliferation, the release of Ni ions from bare NiTi alloy increased with time and reached a higher level, which inhibited endothelial cell function at molecular level, whereas TiN coating improved endothelial cell function.
    Biomaterials 01/2014; 35(24):6195–6205. · 8.31 Impact Factor
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    ABSTRACT: The aim of this study was to investigate the osteoinductive effect of natural hydroxyapatite (NHA). NHA was extracted from pig bones and prepared into disk-like samples. Then, proliferation of mouse bone mesenchymal stem cells (MSCs) cultured on NHA was assessed by the methylthiazoltetrazolium (MTT) assay. Furthermore, microarray technology was applied to obtain the gene expression profiles of MSCs cultured on NHA at 24, 48, and 72 h. The gene expression profile was then comprehensively analyzed by clustering, Gene Ontology (GO), Gene Microarray Pathway Profiler (GenMAPP) and Ingenuity Pathway Analysis (IPA). According to the results of microarray experiment, 8992 differentially expressed genes were obtained. 90 differential expressed genes related to HA osteogenic differentiation were determined by GO analysis. These genes included not only 6 genes related to HA osteogenic differentiation as mentioned in the literatures but also newly discovered 84 genes. Some important signaling pathways (TGF-β, MAPK, Wnt, etc.) were influenced by these genes. Gene interaction networks were obtained by IPA software, in which the scoring values of two networks were highest, and their main functions were related to cell development. The comprehensive analysis of these results indicate that NHA regulate some crucial genes (e.g., Bmp2, Spp1) and then activate some pathways such as TGF-β signaling pathway, and ultimately osteogenic differentiation was induced. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.
    Journal of Biomedical Materials Research Part A 09/2013; · 2.83 Impact Factor
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    ABSTRACT: To explore molecular mechanism of mediation of adsorbed proteins to cell adhesion and growth on biomaterials, this study examined endothelial cell adhesion, morphology and viability on bare and titanium nitride (TiN) coated nickel titanium (NiTi) alloys and chitosan film firstly, and then identified the type and amount of serum proteins adsorbed on the three surfaces by proteomic technology. Subsequently, the mediation role of the identified proteins to cell adhesion and growth was investigated with bioinformatics analyses, and further confirmed by a series of cellular and molecular biological experiments. Results showed that the type and amount of adsorbed serum proteins associated with cell adhesion and growth was obviously higher on the alloys than on the chitosan film, and these proteins mediated endothelial cell adhesion and growth on the alloys via four ways. First, proteins such as adiponectin in the adsorbed protein layer bound with cell surface receptors to generate signal transduction, which activated cell surface integrins through increasing intracellular calcium level. Another way, thrombospondin 1 in the adsorbed protein layer promoted TGF-β signaling pathway activation and enhanced integrins expression. The third, RGD sequence containing proteins such as fibronectin 1, vitronectin and thrombospondin 1 in the adsorbed protein layer bound with activated integrins to activate focal adhesion pathway, increased focal adhesion formation and actin cytoskeleton organization and mediated cell adhesion and spreading. In addition, the activated focal adhesion pathway promoted the expression of cell growth related genes and resulted in cell proliferation. The fourth route, coagulation factor II (F2) and fibronectin 1 in the adsorbed protein layer bound with cell surface F2 receptor and integrin, activated regulation of actin cytoskeleton pathway and regulated actin cytoskeleton organization.
    Biomaterials 05/2013; · 8.31 Impact Factor
  • Yinghua Qu, Yan Huang, Xiaoying Lü
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    ABSTRACT: The aim of the present study is to investigate the molecular effects of Gold nanoparticles (GNPs) on the human dermal fibroblasts-fetal (HDF-f) at the level of protein expression. 20-nm GNPs were prepared using chemical reduction method. After HDF-f were treated with 200 microM GNPs for 1, 4 and 8 h, protein expression profiles were obtained using two-dimensional difference gel electrophoresis (2D-DIGE) and mass spectra (MS) analysis. The obtained differential expressed proteins were analyzed by clustering, gene microarray pathway profiler (GenMAPP) and Ingenuity pathway analysis (IPA) analysis, and verified by western blot. 40 protein spots were filtered with different expression in abundance in all three-culture periods and 24 unique proteins were identified. Bioinformatics analysis results indicated that GNPs might have an influence on the HDF-f in the aspects of signal transduction, actin cytoskeleton, energy metabolism, oxidative stress cell transcription factor, etc. Compared with the gene expression effects induced by GNPs in our previous research, certain relationships at molecular level after HDF-f treated with GNPs were identified. The proteomic analysis used here would also be a useful tool to improve the mechanistic understanding of nanomaterials biocompatibility.
    Journal of Biomedical Nanotechnology 01/2013; 9(1):40-52. · 7.58 Impact Factor
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    ABSTRACT: This work examines the molecular mechanism of action of a class of bactericidal gold nanoparticles (NPs) which show potent antibacterial activities against multidrug-resistant Gram-negative bacteria by transcriptomic and proteomic approaches. Gold NPs exert their antibacterial activities mainly by two ways: one is to collapse membrane potential, inhibiting ATPase activities to decrease the ATP level; the other is to inhibit the subunit of ribosome from binding tRNA. Gold NPs enhance chemotaxis in the early-phase reaction. The action of gold NPs did not include reactive oxygen species (ROS)-related mechanism, the cause for cellular death induced by most bactericidal antibiotics and nanomaterials. Our investigation would allow the development of antibacterial agents that target the energy-metabolism and transcription of bacteria without triggering the ROS reaction, which may be at the same time harmful for the host when killing bacteria.
    Biomaterials 12/2011; 33(7):2327-33. · 8.31 Impact Factor
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    ABSTRACT: Repair of injured spinal cords by regeneration therapy remains an elusive goal. In this paper, a system aiming at remote motor function restoration with 3G technology has been presented. This system contains three principle sub-systems: neural signal detecting, communication, and functional electrical stimulation. Functions of each sub-system have been introduced. At the end of this paper, electrical test result of the system has been given, which is qualified for the further animal experiments.
    Information Science and Technology (ICIST), 2011 International Conference on; 04/2011
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    ABSTRACT: To evaluate the biomechanical properties and biocompatibility of natural hydroxyapatite/chitosan (HA/CS) composites. The natural HA/CS composites with a different proportion of HA and CS were prepared by the cross-linking method, and then the compressive strength, microstructure and pH values of extracts from these composites were measured by SEM and pH meter, respectively. Subsequently, the biocompatibility of the composites was evaluated by means of a series of biological tests, including MTT, acute systemic toxicity, heat source, and hemolysis tests in vitro. The chitosan content in the composites had significantly influenced the mechanical properties and microstructure of the composites. The pH value of the composite extract was approximately 7.0, which was very close to that of human plasma. Furthermore, the natural HA/CS composites showed no cytotoxicity, irritation, teratogenicity, carcinogenicity and special pyrogen. These results indicated that the natural HA/CS composite may be a potential bone repair material.
    Journal of applied biomaterials & biomechanics (JABB) 03/2011; 9(1):11-8. · 1.54 Impact Factor
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    ABSTRACT: Microelectrode arrays (MEAs) for stimulation and signal recording of in vitro cultured neurons are presented. Each MEA is composed of 60 independent electrodes with 59 working ones and one reference one. These electrodes are divided into 30 pairs. Through each pair of electrodes, four independent states can be realized to define the accessing modes of neurons cultured on the surface of the electrodes. A total MEA covers an area of 10 mm×10 mm. MEAs are fabricated in a silicon-based semiconductor process. An implemented MEA is bonded on a specially designed printed-circuit-board (PCB) and surrounded by a culture chamber. An impedance measurement has been made to verify the electrical characteristics of MEAs. The surface was modified to enhance the biocompatibility. A series of PC12 cells culture experiments validates the effectiveness of the modification. An extracellular signal recording experiment with acetylcholine (Ach) as a stimulant has been carried out, and the results show the feasibility of MEAs for extracellular action potential recording. Extracellular electrical stimulation and recording experiments have been carried out too. They indicate that MEAs can be used for extracellular stimulation, recording, simultaneous stimulation and recording, and isolation of PC12 cells network cultured in vitro.
    Sciece China. Information Sciences 01/2011; 54:2199-2208. · 0.71 Impact Factor
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    ABSTRACT: A neural stimulating circuit and a neural signal detecting circuit designed for a monolithic integrated MEA (micro-electrode array) are described. Two OPAs (operational amplifier) used as the basic cells of the circuits were designed. One is a telescopic OPA with low noise and low power, the other one is with rail-to-rail swing and constant gm. The circuits are realized in a standard 0.5-μm CMOS process (CSMC, Wuxi, China) and the test results of the circuits will be described.
    Bioelectronics and Bioinformatics (ISBB), 2011 International Symposium on; 01/2011
  • Yamin Yang, Yinghua Qu, Xiaoying Lü
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    ABSTRACT: In order to investigate the molecular effects of gold nanoparticles (GNPs) and cell interaction, after human dermal fibroblasts-fetal (HDF-f) treated with GNPs for 1, 4 and 8 h, the cytotoxicity was evaluated with methylthiazoltetrazolium (MTT) assay. Flow cytometry experiment was used to assess effects of GNPs on cell cycle and apoptosis. Differentially expressed genes in HDF-f treated with GNPs were obtained using gene expression profile microarray. The gene differential expression profile was analyzed by clustering, Gene Ontology (GO) and biological pathway. The results from these analyses were integrated to comprehensively interpret the data gained from microarray. It suggests that the exposure of HDF-f to GNPs might lead to the disturbance of cell cycle regulation, cellular oxidative stress and affect regulation of actin cytoskeleton, and other cellular activities such as cell adhesion, energy metabolism and signal transduction may be also affected. Compared with the cytotoxicological mechanisms induced by Ni2+ from our previous research and by GNPs from the present study, different underlying biological processes and gene regulations were found. The integration of microarray and bioinformatics analysis can provide a specific and efficient routine to discuss molecular effects of cellular response to biomaterials.
    Journal of Biomedical Nanotechnology 06/2010; 6(3):234-46. · 7.58 Impact Factor
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    ABSTRACT: To reveal molecular mechanisms of the interaction between Ni2+ and cells, cDNA microarray technology and GenMAPP analysis were utilized to investigate changes of gene expression profile and identify significant biological pathways in mouse fibroblast cells (L-929) treated by 100 microm Ni2+ for 12, 24, 48 and 72 h, respectively. The microarray data was validated by real-time PCR. Methylthiazoltetrazolium (MTT) analysis and flow cytometry experiment were used to assess the cellular response of L-929 cells to Ni2+. It was found that six main biological pathways were affected by Ni2+ with 118 differentially expressed genes involved. Further analysis illuminated that the exposure of cells to Ni2+ may evoke series of cellular responses to hypoxia by regulating hypoxia-inducible gene expression and cause irreversible DNA damage. Cell cycle pathway analysis results showed DNA replication in S phase could be inhibited by Ni2+ which was consistent with the data gained from flow cytometry experiment. Compared to previous researches based on conventional molecular biology experiments, the present work has not only indirectly validated the findings of other groups but also obtained several discoveries related to cell-Ni2+ interaction, such as inhibition of electron transport chain and accumulation of extracellular matrix (ECM) collagens. The routine of the present study not only can analyze gene expression profile but also may provide a more convenient and efficient approach to explain molecular mechanisms of cell-biomaterial interaction.
    Biomaterials 03/2010; 31(8):1965-73. · 8.31 Impact Factor
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    ABSTRACT: Reflectometry interference spectroscopy (RIfS) is known as a highly sensitive and robust technique for direct, label-free detection of the interaction of biomacromolecules in real time and in situ. The aim of the present study was to investigate the competitive protein adsorption on the surface of fluorocarbon end-capped poly(carbonate) urethane (PCUF) and polystyrene (PS) based on the RIfS method. The surface energy and microstructures of PCUF and PS were characterized by contact angle measurement and atomic force microscopy. Interfacial energies between these surfaces and the proteins were then calculated. The protein adsorption experiments were carried out with both single solution and ternary solutions composed of albumin, fibrinogen and immunoglobulin-G (IgG). The results of surface characterization showed that PCUF was more hydrophilic than PS with a smaller surface energy, and micro-phases separation of PCUF was observed. RIfS analysis results revealed that more albumins, less fibrinogen and IgG were detected on the PCUF surface compared with PS after simplex and competitive protein adsorption, which indicated that PCUF had a preferential adsorption for albumin. The special morphology, smaller surface energy and calculated interfacial energies between PCUF and proteins may be responsible for the better blood compatibility of PCUF compared to PS. The results suggest that RIfS could serve as a novel, effective method for studying the competitive protein adsorption on biomaterial surfaces.
    Acta biomaterialia 12/2009; 6(6):2083-90. · 5.68 Impact Factor
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    ABSTRACT: The aim of this study is to improve hippocampal cell adhesion on silicon (Si) surfaces by surface modification via a chemical method. Collagen and chitosan were first immobilized on a Si surface through a bridging layer of (3-aminopropyl) triethoxysilane and 1-ethyl-3-(3-dimethyllaminopropyl) carbodiimide. The modified Si surface was then characterized by contact angle measurement, Fourier transform infrared spectroscopy, x-ray photoelectron spectroscopy and atomic force microscopy. The amounts of protein adsorbed on the bare Si surface and collagen/chitosan-modified Si surface were measured by a modified Coomassie brilliant blue protein assay. The cell adhesion behavior was then assessed by a microscopy. The results showed that after the surface modification with the collagen/chitosan compound the protein adsorption on Si surfaces decreased while the adhesion ability of hippocampal cells increased.
    Biomedical Materials 11/2009; 4(6):065004. · 2.92 Impact Factor
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    ABSTRACT: The aim of the present study was to investigate the effect of chitosan modification of silicon (Si) on protein adsorption, cell adhesion and cell proliferation. Chitosan was first immobilized on the Si surface through a (3-aminopropyl)triethoxysilane (APTES) bridge. The surface was then characterized by contact angle measurement, atomic force microscopy (AFM), x-ray photoelectron spectroscopy (XPS) and energy dispersive x-ray spectroscopy (EDX). The amount of protein adsorbed on the native Si and chitosan-modified Si surface was evaluated by a modified Coomassie brilliant blue (CBB) protein assay. The adhesion and proliferation behavior of L-929 and pc12 cells were then assessed by microscopy and methylthiazoltetrazolium (MTT) tests. The results showed that the chitosan modification could resist protein adsorption and inhibit the adhesion and proliferation of two kinds of cells on Si.
    Biomedical Materials 08/2009; 4(4):044103. · 2.92 Impact Factor
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    ABSTRACT: This article concerns the investigation of blood protein adsorption on carbon paper and multi-wall carbon nanotubes (MWCNTs). Mouse fibroblast cell adhesion and growth on MWCNTs was also studied. The results showed that fibrinogen adsorption on carbon paper was much lower than that on MWCNTs, which means that platelets readily aggregate on the surface of MWCNTs. Mouse fibroblast cells implanted on MWCNTs tended to grow more prolifically than those implanted on carbon paper. The cell concentration observed on MWCNTs increased from 1.2x10(5)/mL for a single day culture to 2x10(5)/mL for a 7-day culture. No toxicity reaction was observed during the culturing period. These results indicated that MWCNTs possessed excellent tissue compatibility.
    Science in China Series C Life Sciences 06/2009; 52(5):479-82. · 1.61 Impact Factor
  • Yinghua Qu, Xiaoying Lü
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    ABSTRACT: The unique physicochemical properties of nanoparticles make them promising substrates for application in the medical area. As there are no safety regulations yet, concerns about future health problems are rising. This study was conducted to prepare approximately 20 nm gold nanoparticles (GNPs) by a chemical reduction method and evaluate their cytotoxicity by MTT assay using human dermal fibroblasts-fetal (HDF-f). 10-50 nm GNPs could be obtained in redistilled water by varying the amount of sodium citrate. MTT results showed that approximately 20 nm GNPs did not cause cell death at a maximum concentration of 300 microM but affected the morphology of HDF-f when their concentration increased.
    Biomedical Materials 05/2009; 4(2):025007. · 2.92 Impact Factor
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    ABSTRACT: The presence of neural signals is the most important feature of animals' life. Monitoring, analysis and regeneration of neural signals are important for the rehabilitation of paralyzed patients. In this paper, the neural signal regeneration between the proximal and the distal end of an injured nerve is introduced. In the experiment a microelectronic module is used as a channel bridge. The regeneration of nerve signals is realized from one toad's sciatic nerve to another's. Corresponding neural signals and EMG were recorded and analyzed. It will be a reference to further study on the neural signals and the relationship between a neural signal and the muscle locomotion.
    Conference proceedings: ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference 01/2009; 2009:5953-6.
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    ABSTRACT: Due to the difficulty in spinal cord regeneration with biological methods, the microelectronic neural bridge, a new concept based on microelectronic technology, is presented. The microelectronic system has been realized in the forms of hybrid and integrated circuits. The integrated circuits for neural signal detection, stimulation, and regeneration are realized in a CMOS process. In animal experiments with 100 toads, 48 rats, and 3 rabbits, nerve signals have been successfully detected from spinal cords and sciatic nerves, and functional electrical stimulation has been carried out for spinal cords and sciatic nerves. When the microelectronic system is bridged between the controlling and stimulated nerve, the relevant motion of legs and nerve signal waveforms, which are stimulated by the evoked or spontaneous nerve signal through such a system, have been observed. Therefore, the feasibility of the presented method was demonstrated.
    Progress in Natural Science - PROG NAT SCI. 01/2009; 19(10).